Research advances in exosomes involved in the occurrence, development and clinical diagnosis and treatment of sepsis / 中华危重病急救医学

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host immune response to infection. The development of sepsis is accompanied by the secretion of exosomes by a variety of cells, including non-coding RNA, metabolic small molecules and proteins, which play an important role in immune inflammatory response, oxidative stress, and coagulation dysfunction. The rapid development of new detection technologies has promoted the application of exosomes in the early warning, severity stratification, treatment effect and prognosis evaluation of sepsis. This article reviews the new detection technology of exosomes, the involvement of exosomes in the pathological progress of sepsis, and the latest progress in the early diagnosis, disease assessment and treatment of sepsis, in order to provide new ideas for the diagnosis and treatment of sepsis.

Clinical and imaging analysis of neurological complications in critically ill children infected with SARS-CoV-2 Omicron / 中华危重病急救医学

OBJECTIVE@#To summarize clinical predictors and imaging characteristics of critically ill children infected with SARS-CoV-2 Omicron with neurological complications in Shenzhen during the peak of the first round of infections.@*METHODS@#The clinical data of 11 critically ill children with neurological complications infected with SARS-CoV-2 Omicron in Shenzhen Children's Hospital from December 12 to 31, 2022, were retrospectively collected and analyzed. Laboratory test results related to liver parenchymal injury, histiocytic injury, inflammation, and coagulation function were collected, and imaging characteristics including CT and/or magnetic resonance imaging (MRI) were analyzed. The differences in CT/MRI score, acute necrotizing encephalopathy severity scale (ANE-SS) score and total score (CT/MRI score + ANE-SS score) were compared between the two groups with different prognosis during hospitation.@*RESULTS@#Among 11 children, 7 were male and 4 were female. The age ranged from 10 months to 16 years. There were 5 cases of acute necrotizing encephalopathy (ANE) and 6 cases of acute fulminant cerebral edema (AFCE). During hospitalization, 3 patients survived and 8 patients died of multiple organ dysfunction syndrome (MODS), including 2 cases of ANE and 6 cases of AFCE. All cases had fever (> 38.5 centigrade), and 3 cases had ultra-high fever (> 41 centigrade). Within 48 hours of onset, all cases had disorders of consciousness and 9 cases had seizures. The 8 dead children had complications with multisystem involvement, including shock, respiratory failure, disseminated intravascular coagulation (DIC), liver failure, renal failure or myocardial damage, and the laboratory predictors related to hepatocellular injury [alanine aminotransferase (ALT), aspartate aminotransferase (AST)], histocyte injury [creatine kinase (CK), lactate dehydrogenase (LDH)], inflammation [procalcitonin (PCT), interleukin-6 (IL-6), serum ferritin (SF)], coagulation function (D-dimer) and blood glucose (Glu) increased in different quantities, of which PCT was specifically increased in 6 cases with AFCE, PLT was specifically decreased in 3 cases with AFCE, and ALT and LDH were significantly increased in 2 cases with ANE. Imaging analysis showed subarachnoid hemorrhage, basal ganglia and thalamus lesions in all 6 cases with AFCE, while thalamus lesions in all 5 cases with ANE. The ANE-SS score of 8 deceased children ranged from 2 to 7 (of which 6 cases were ≥ 5), and the ANE-SS score of 3 surviving children ranged from 0 to 2. Eight dead children had a CT/MRI score of 1-4 (of which 6 cases were 4), and 3 surviving children had a CT/MRI score of 1-2 (of which 2 cases were 1). The total score of 8 deceased children was 6-10 (of which 6 cases ≥ 8), and 3 surviving children was 1-4.@*CONCLUSIONS@#The neurological complications of critically ill children infected with SARS-CoV-2 Omicron in Shenzhen progressed rapidly to ANE and AFCE, with high mortality. High fever (> 40 centigrade), convulsion/disturbance of consciousness, and multiple organ failure were the most common symptoms in ANE and AFCE cases. PCT increased and PLT decreased specifically in AFCE cases. Poor prognosis (death) was more common in age < 4 years old, predictors of ALT, AST, CK, LDH, PCT, D-dimer, Glu, IL-6 increased significantly, PLT decreased significantly. The common imaging feature of ANE and AFCE is the involvement of dorsal thalamus, a new imaging sign of AFCE (subarachnoid hemorrhage) was found. The higher the ANE-SS score, CT/MRI score and total score, the greater the risk of death.

Multimodal magnetic resonance imaging for assessment of motor function after hemispherectomy in children with refractory epilepsy / 中华实用儿科临床杂志

Hemispherectomy (HS) is an effective surgical therapy to treat refractory epilepsy caused by diffuse hemispheric disorders.After HS surgery, the seizures are often well controlled in patients, and the bilateral limb motor function improves even recovers in some children.This result reveals the strong neuronal plasticity of the brain.The brain, especially of young children, can achieve functional reorganization and cortical remodeling after extensive damage.Multimodal magnetic resonance imaging techniques can jointly analyze the structure and function of the brain and associated neuroimaging features to reveal the neurophysiological mechanisms underlying improved motor function.In this paper, the progress of multimodal magnetic resonance imaging research on motor function alterations in children after hemispherectomy was reviewed.

Practice and thinking of pre-hospital emergency support for the 2022 Beijing Winter Olympic Games / 中华医院管理杂志

Under the leadership of the Beijing Winter Olympic Organizing Committee and the Beijing Municipal Health Commission, the Beijing Emergency Center, as the designated medical institution for the 2022 Beijing Winter Olympic Games, has completed the first aid support task of this Winter Olympic Games with other medical institutions. The author systematically analyzed the development of each link in the pre-hospital emergency support for the 2022 Beijing Winter Olympic Games, summarizes the key links of the entire Winter Olympics cycle, such as the construction of the organizational system, the formulation of support plans, and the training of support personnel, and analyzed the results of related work, so as to provide reference for the pre-hospital emergency support for China to host large-scale international events in the future.

Brain dynamic functional connectivity between default mode network and executive control network by resting state functional MRI in patients with alcohol use disorder / 中华放射学杂志

Objective:To investigate the changes of dynamic functional connectivity between the default mode network (DMN) and executive control network (ECN) in the resting state in patients with alcohol use disorder (AUD).Methods:From September 2018 to June 2019, 23 cases of AUD group and 24 cases of healthy control (HC) group matched with age, gender, education level and handedness were collected at Renmin Hospital of Wuhan University. Mini-mental state examination (MMSE) and Michigan alcoholism screening test (MAST) were performed in all subjects for cognition and alcohol dependence score. All the subjects underwent T 1WI-3D structural imaging and resting state functional MRI (rs-fMRI) examination. Group spatial independent component analysis (ICA) was used to select the independent components of DMN and ECN. Then dynamic changes in the functional connectivity between the DMN and the DMN were obtained by sliding window approach and clustering method. Finally, the independent sample t test was used to compare the difference of general clinical data between the two groups, the linear correlation analysis was conducted in the parameter value and MMSE and MAST scores. Results:Compared with the HC group, the static functional connectivity analysis showed that the precuneus and posterior cingulate gyrus of the DMN were enhanced in the AUD group ( P=0.016, t=2.496). The DMN and ECN functional connectivity showed four different brain activity states, the proportion of state1 increased by 6.81% and state2 decreased by 6.83% in the AUD group, state3 and state4 were relatively stable. In state1, the internal functional connectivity of the DMN in the AUD group was enhanced, while the functional connectivity between DMN and ECN was mainly enhanced. In state2, the internal functional connectivity of the ECN was enhanced, and the connectivity between the DMN and ECN was mainly weakened. The mean dwell of state2 in the AUD group was negatively correlated with the MAST score ( r=-0.433, P=0.039). Conclusions:Dynamic functional connectivity patterns between DMN and ECN have been changed in patients with AUD. Dynamic functional connectivity can reveal transient changes in brain activity, which can provide certain imaging evidence for finding changes in AUD deep brain activity.

Study on the development of the standardized system of pre-hospital rescue and transfer / 中华医院管理杂志

Pre-hospital rescue is key to the emergency medical system. Based on the current pre-hospital emergency standardized system construction in China, the authors explored the standardization of pre-hospital emergency system construction, command dispatch and emergency service quality control standardization, pre-hospital classification standardization, pre-hospital emergency service capacity standardization, pre-hospital emergency and intra-hospital emergency connection standardization, standardized training for pre-hospital emergency doctors and nurses. These efforts aim to achieve such rescue and transfer criteria for patients, as " vicinity, urgency, professional needs, and intension of both patients and their families" . Such criteria if met can further reduce emergency response time and shorten the emergency radius, hence improving emergency medical services.

Design and construction of an intelligent pre-hospital emergency synergy system / 中华医院管理杂志

As a key part of the emergency medical system,pre-hospital emergency service proves critical for critical care,higher pre-hospital care success rate,improvement of patient outcome,and promotion of health recovery.This paper analyzed the status quo of pre-hospital emergency services information,discussed the application of information technology in pre-hospital industries including command and dispatch system,ambulance real-time positioning and tracking system,pre-hospital emergency video surveillance system,medical record system,electronic patient health file system,electronic payment system,and data mining and analysis system.Furthermore,it also discussed the prospect of sizably upgrading prehospital emergency service and building intelligent pre-hospital emergency coordination system.

Design and construction of an intelligent pre-hospital emergency synergy system / 中华医院管理杂志

As a key part of the emergency medical system, pre-hospital emergency service proves critical for critical care, higher pre-hospital care success rate, improvement of patient outcome, and promotion of health recovery. This paper analyzed the status quo of pre-hospital emergency services information, discussed the application of information technology in pre-hospital industries including command and dispatch system, ambulance real-time positioning and tracking system, pre-hospital emergency video surveillance system, medical record system, electronic patient health file system, electronic payment system, and data mining and analysis system.Furthermore, it also discussed the prospect of sizably upgrading pre-hospital emergency service and building intelligent pre-hospital emergency coordination system.

Effect of Simvastatin on expressions of myocardial chromogranin A and apoptosis signal-regulating kinase 1 of immature rabbits with chronic heart failure / 中华实用儿科临床杂志

Objective To observe the influence of Simvastatin on immature rabbit model of chronic heart failure(CHF),and to explore the possible protective mechanism of Simvastatin for the rabbits with CHF.Methods Thirty immature male rabbits were divided into 3 groups randomly:control group,heart failure group (HF group)and Simvastatin group(SIM group),10 rabbits in each group.The models of CHF were established by injecting Adrinmycin via the auricular vein of rabbits (1.5 mg/kg,once 1 week,for 12 weeks).The control group were injected the same amount of 9 g/L saline.SIM group were given both injection of Adrinmycin and Simvastatin [1.5 mg/(kg · d)for 12 weeks].The immature rabbit's cardiac function and myocardial morphology changes were evaluated.The expressions of chromogranin A (CgA) and apoptosis signal-regulating kinase 1 (ASK1) were evaluated.Results (1) In control group,the immature rabbits were all alive;in the other 2 groups,most immature rabbits were depressed and sluggish.The survival rate of HF group was 60％,while in SIM group the survival rate was 80％.(2)Compared with the control group,the left ventricular ejection fraction in HF group and SIM group decreased significantly [(40.05 ± 6.74)％,(50.18 ± 5.73) ％ vs.(65.93 ± 5.65) ％,all P ＜ 0.01],while in SIM group was higher than that of HF group,and the difference was significant (P ＜ 0.05);compared with HF group,the left ventricular end diastolic diameter and left ventricular end systolic diameter decreased in SIM group [(13.48 ± 1.24) mm vs.(16.23 ± 2.82) mm;(9.87 ± 0.85) mm vs.(11.13 ± 1.21) mm],and the differences were significant (all P ＜ 0.05).(3) Compared with the control group,the expression of CgA (mean optical density 142.24 ± 17.14,127.93 ± 12.12 vs.78.65 ± 6.78,P ＜ 0.05;integrated optical density 1 422.41 ± 167.34,1 279.37 ± 118.15 vs.786.54 ± 75.84,P ＜ 0.05) and ASK1 (mean optical density 140.32 ± 18.65,115.48 ± 12.30 vs.69.85 ± 6.54,P ＜ 0.05;integrated optical density 1 403.23 ± 165.67,1 158.79 ± 137.81 vs.698.58 ± 64.51,P ＜ 0.05) increased in the HF group and SIM group.While the expression in the SIM group decreased significantly compared with that of the HF group,and the difference was significant (P ＜ 0.05).Conclusions Simvastatin can improve cardiac function of immature rabbits with CHF.The mechanism of SIM may depress the expressions of CgA and ASK1.

Effects of Simvastatin on myocardial apoptosis and oxidative stress mechanism in immature rabbits with chronic heart failure / 中华实用儿科临床杂志

Objective To observe the effects of Simvastatin on myocardial apoptosis and oxidative stress mechanism in immature rabbits with chronic heart failure.Methods Thirty-six male New Zealand big-eared immature rabbits were randomly divided into 3 groups:Adriamycin(ADR) ± Simvastatin group(ADR-s group,n =12),in which ADR(1.5 mg/kg) received injection via the auricular vein of rabbits weekly,and the rabbits received oral Simvastatin [1.5 mg/(kg · d)] simultaneously for 12 weeks;ADR group (n =12),in which the rabbits received ADR like ADR-S group,and 9 g/L saline instead of Simvastatin;control group (CON group,n =12),which received the same amount of 9 g/L saline.Echocardiography examination was performed in 13th week.Myocardial fibrosis degree was detected by using MASSON staining,and the myocardial apoptosis was detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling.Colorimetric method was used to detect the myocardial concentration superoxide dismutase (SOD) and malondialdehyde (MDA).Enzyme-linked immunosorbent assay was used to detect serum B-type brain natriuretic peptide (BNP) level.Results (1) In CON group,the immature rabbits were all alive.Four rabbits died in ADR group,and the survival rate was 66.7％,while 2 rabbits died in ADR-s group,and the survival rate was 83.3％.(2)Compared with CON group,the left ventricular end diastolic diameter (LVEDd) and left ventricular end systolic diameter (LVESd) in ADR-s group and ADR group increased [(11.90 ±1.09) mm,(ll.34 ±0.92) mm vs.(10.73 ±0.48) mm;(9.80 ±0.88) mm,(8.47 ± 1.23) mm vs.(7.31 ±0.36) mm];left ventricular fractional shortening(LVFS) and left ventricular ejection fraction(LVEF) decreased [(17.65 ± 1.70)％,(22.58 ± 2.19)％ vs.(31.79 ± 2.58) ％;(41.35 ± 3.19) ％,(49.17 ± 3.53) ％ vs.(64.34 ± 3.97) ％],and all the differences were significant(all P ＜ 0.05);LVEDd and LVESd in ADR-s group were lower than those of ADR group,while LVEF and LVFS in ADR-s group were higher than those of ADR group,and the differences were significant(all P ＜ 0.05).(3)MASSON staining:compared with ADR group,there was less myocardial cell hyperplasia of fibrous tissue in ADR-s group.(4) Compared with CON group,the apoptosis index was higher in ADR and ADR-s group [(34.25 ±11.13) ％,(24.00 ±6.85)％ vs.(16.58 ± 5.34)％],but ADR-s group had less than ADR group,and the differences were significant (all P ＜ 0.05).(5) Compared with ADR group,SOD activity of ADR-s group was higher [(13.40 ± 2.68) kU/L vs.(10.66 ± 2.99) kU/L],but MDA content was lower [(5.67 ± 1.36) μmol/mg vs.(7.08 ±0.98) μmol/mg],and the differences were significant (all P ＜0.05).(6) Serum BNP level in ADR group and ADR-s group was higher than that of the CON group[(33.28 ±9.58) μg/L,(26.71 ±6.72) μg/L vs.(13.56 ±2.82) μg/L],while was higher in ADR group than that of ADR-s group,and the differences were significant (all P ＜ 0.05).Conclusions Simvastatin can protect cardiac function of immature rabbits with chronic heart failure.The possible mechanism may be the up-regulation of myocardial SOD activity,reduction of cell lipid peroxidation and inhibition of myocardial apoptosis.

Improvement Effect of Minocycline on Cognitive Dysfunction Induced by Old RBCs Transfusion in Rats / 中国药师

Objective:To observe the effect of old RBCs transfusion on cognitive function in rats and the improvement effect of mi -nocycline.Methods: Male SD rats at the age of 6 months were randomly divided into 4 groups.The RBCs were obtained from male rats by centrifuging the total blood and stored at 4℃.The rats of fresh RBCs group (group F) were transfused with the RBCs stored for 1 day.The rats of old RBCs group (group O) were transfused with the RBCs stored for 7 days.The rats of treatment group (group T) received 40 mg· kg-1 minocycline with intraperitoneal injection before the transfusion .The rats of the control group ( group C) were transfused with the normal saline .The brain levels of IL-1βand IL-6 were determined with Quantikine ELISA kits in 24 hours after the blood transfusion (n=6).The rats were subjected to Barnes maze tests after 1 week of the blood transfusion (n=10).Results:The brain levels of IL-1βand IL-6 in group O were higher than those in group C and F (P<0.05), which were lower in group T than those in group O(P<0.05).The rats of group O spent longer time finding the target box than those of group C and F in the Barnes maze (P<0.05), and the time was shorter in group T than that in group O (P<0.05).Conclusion: Old RBCs transfusion plays a role in neuro-inflammation and induces cognitive dysfunction in rats , which may be improved by minocycline .

Protective Effects of Memantine on Isofluane￣induced Decrease of Proliferation in Neural Stem Cells / 医药导报

Objective To investigate the protective effects of memantine on isofluane￣induced decrease of proliferation in neural stem cells ( NSCs) and the potential mechanisms in vitro. Methods Neural stem cells were isolated from rat hippocampi (postnatal day 1) and grew in culture. Cultured NSCs were randomly divided into the control ( Group Control), Vehicle (Group Vehicle), Isoflurane ( Group Iso), Isoflurane +Memantine ( Group Iso +Mem) and Isoflurane + Memantine +LY294002 groups (Group Iso+Mem+LY).Proliferation was assessed by cell counting and BrdU incorporation.Western blot was conducted to detect protein expression of phospho￣Akt. Results Compared with the control group,BrdU incorporation and phospho￣Akt expressions in neural stem cells significantly declined after 2.4% isoflurane exposure for 6 h (P<0.01).However, isofluane￣induced decrease of BrdU incorporation and phospho￣Akt expressions was attenuated by the treatments of memantine (P<0.01)). It was showed that Akt inhibitors LY294002 reversed the protective effects on neural stem cells proliferation by memantine(P<0.01). Conclusion The results suggest that memantine treatment might attenuate isofluane￣induced decrease of proliferation in neural stem cells via Akt signaling pathway.

The effects of acupuncture combined with speech therapy on aphasia caused by stroke: clinical and fMRI study / 中华物理医学与康复杂志

Objective To observe and compare the effects of acupuncture and acupuncture plus speech therapy on activation of the brain areas in aphasic patients by use of oxygenation level dependent-functional magnetic resonance imaging (BOLD-fMRI).Methods Twenty patients with aphasia caused by stroke were randomized into two groups by use of random number table (10 cases in each group):an experimental group subject to acupuncture treatment combined with speech therapy,and a control group subject to speech therapy only.All the cases were dextromanuality.On admission and after 1 month of treatment,BOLD-fMRI was used to test signals of the activated brain areas of both group,and Aphasia Battery of the Chinese (ABC) was employed to evaluate the changes of speech ability of the patients.Results During the study,1 case from control group was unable to do the post-intervention evaluation due to onset of the second stroke.The effective rates of the control and experimental group were 55.56％ and 100.00％,respectively,and recovery of verbal ability in experimental group was significantly better than in control group (P ＜ 0.05).The active volume and extent in brain were significantly increased in both groups (P ＜0.05),and a comparison between the two groups showed that the changes in activation volume and extent of the brain were significantly greater extensive in experimental group than in the control group,especially in bilateral frontal lobe,cuneus,posterior cingulate gyrus,lingual gyrus,occipital lobe,splenium of corpus callosum,cerebellar hemisphere,and the left precentral gyrus,post-central gyrus,paracentral lobule,temporal lobes,angular gyrus,precuneus,and the right hippocampus,parahippocampus gyrus.Conclusion Acupuncture combined with speech therapy could cause changes in activation patterns of the brain areas,which may contribute to the improvement of verbal ability of the aphasic patients.

Effect of lithium chloride pretreatment on isoflurane-induced cognitive dysfunction and inflammatory response in hippocampus in aged rats / 中华麻醉学杂志

Objective To evaluate the effect of lithium chloride (LiCl) pretreatment on isoflurane-induced cognitive dysfunction and inflammatory response in hippocampus in aged rats.Methods Eighty 20-month-old male Sprague-Dawley rats,weighing 350-400 g,were randomly assigned into 4 groups (n =20 each):control group (group C),1.4％ isoflurane group (group I),100 mg/kg LiCI + 1.4％ isoflurane group (group L+ I),and 100 mg/kg LiC1 group (group L).Group I was exposed to 1.4％ isoflurane in 30％ O2-70％ N2 for 6 h,while group C was exposed to 30％ O2-70％ N2 only.LiCl 100 mg/kg was injected intraperitoneally once a day for 3 consecutive days and isoflurane anesthesia was performed on 4th day in group L + I.LiCl 100 mg/kg was injected intraperitoneally once a day for 3 consecutive days and then the rats inhaled 30％ O2-70％ N2 for 6 h on 4th day in group L.Blood samples were taken immediately after the end of anesthesia for blood gas analysis.Hippocampi were isolated 24 h after the end of anesthesia for determination of the expression of glycogen synthase kinase-3β (GSK-3β) and acetyl-NF-κB (Lys310) (by Western blot) and TNF-α,IL-1β and IL-6 mRNA (by RT-PCR).The levels of TNF-α,IL-1β and IL-6 were determined by ELISA and the contents of TNF-α,IL-1β and IL-6 were calculated.The cognitive function was assessed on 2nd day after the end of anesthesia.Results Compared with group C,the expression of GSK-3β and acetyl-NF-κB (Lys310) was significantly up-regulated,the expression of TNF-α,IL-1β and IL-6 mRNA and contents of TNF-α,IL-1β and IL-6 were increased,the escape latency was prolonged,and the time of staying at the original platform quadrant was shortened in group I (P ＜ 0.05).Compared with group I,the expression of GSK-3β and acetyl-NF-κB (Lys310) was significantly down-regulated,the expression of TNF-α,IL-1β and IL-6 mRNA and contents of TNF-α,IL-1β and IL-6 were decreased,the escape latency was shortened,and the time of staying at the original platform quadrant was prolonged in group L + I (P ＜ 0.05).Conclusion LiC1 pretreatment can improve isoflurane-induced cognitive dysfunction and inhibition of inflammatory response in hippocampus is involved in the mechanism in aged rats.

Fractional amplitude analysis of low frequency fluctuation in alcohol dependent individuals : a resting state functional MRI study / 中华放射学杂志

Objective To explore brain activity features during the resting state in alcohol dependent individuals,and study the relationship between the brain activity features and alcohol dependent individuals' clinical symptoms.Methods Twenty-four alcohol dependent individuals and 22 healthy control subjects,well matched in gender,age,education and handedness,were enrolled as the alcohol dependent group and control group respectively.AGE 3.0 T MR scanner was used to acquire all the subjects' resting state data. DPARSF software was used to process resting functional MRI data,and then the whole brain fractional amplitudes of low frequency fluctuation (fALFF) data were acquired.Two-sample t test statistical analysis was made to access fALFF difference between the two groups. Results In comparison with the control group,the alcohol dependent group showed reduced fALFF in bilateral medial prefrontal gyrus,right inferior occipital gyrus,left precuneus,left inferior temporal gyrus,and left posterior lobe of cerebellum (0.64-1.69 vs.0.87-1.78,t =- 4.23- - 2.79,P ＜ 0.05 ). fALFF was increased in the alcohol dependent group at the anterior cingulate,bilateral inferior frontal gyrus,right middle frontal gyrus,bilateral insular lobe,bilateral dorsal thalamus ( 0.86-1.82 vs. 0.76-1.58,t =3.56-3.96,P ＜ 0.05 ).Conclusion Alcohol dependent individuals had abnormal activity at the bilateral prefrontal lobe,anterior cingulate,bilateral dorsal thalamus,bilateral insular lobe,left posterior lobe of cerebellum et al,during the resting state,and these abnormal activities might be related with clinical manifestation and pathophysiology.

Effect of melatonin on ketamine-induced apoptosis in hippocampal neurons of fetal rats / 中华麻醉学杂志

Objective To investigate the effect of melatonin on ketamine-induced apoptosis in hippocampal neurons of fetal rats.Methods Sixteen to eighteen day pregnant Sprague Dawley rats were anesthetized.The fetal rats were obtained under sterile condition and decapitated.The hippocampal neurons were isolated and primary cultured for 5 days.The primary cultured neurons were randomly divided into 5 groups (n =6 each):control group (group C),ketamine group (group K),and 1.0,2.5 and 5.0 mmol/L melatonin groups (groups M1-3 respectively).Ketamine with the final concentration of 1 000 μmol/L was added to the culture medium and the neurons were incubated for 3 h in group K.In groups M1-3,1.0,2.5 and 5.0 mmol/L melatonin were added to the culture medium,respectively,at 60 min before the addition of ketamine,and the neurons were incubated for 3 h.While the equal volume of normal saline was added instead in group C.The neuronal viability during the developmental phase was assessed by MTT assay.The mitochondrial membrane potential (Ψm) was measured by flow cytometry.The expression of cAMP response element binding protein phosphorylation (p-CREB (Ser133)),Bcl-2,Bax,and cytochrome C was detected by Western blot.Results Compared with group C,the neuronal viability and Ψm were significantly decreased,and the expression of p-CREB and Bcl-2 was down-regulated,while the expression of Bax and cytochrome C was up-regulated in group K (P ＜ 0.05).Compared with group K,Ψm was significantly increased in groups M2 and M3,and the neuronal viability was significantly increased,the expression of Bcl-2 was up-regulated,while the expression of Bax and cytochrome C was down-regulated in groups M1-3 (P ＜ 0.05).Conclusion Melatonin can protect the hippocampal neurons of fetal rats from apoptosis triggered by ketamine via regulating the expression of Bcl-2 and Bax,stabilizing Ψm,inhibiting the release of cytochrome C from mitoehondria,and preventing apoptosome formation.

Effect of melstonin on isofurane snesthesis-induced cognitive dysfunction in sged rsts / 中华麻醉学杂志

Objective To investigate the effect of melatonin on isoflurane anesthesia-induced cognitive dysfunction in aged rats.Methods Seventy-five male SD rats,aged 18-20 months,weighing 350-400 g,were randomly assigned into 5 groups(n =15 each):control group(group C),1.5％ isoflurane group(group Ⅰ),melatonin 5 mg/kg group(group M1),melatonin 10 mg/kg group(group M2)and melatonin 20 mg/kg group(group M3).Group G inhaled a gas mixture of oxygen and air for4 h and group 1 inhsled 1.5％ isoflurane for4 h.Melatonin 5,10 and 20 mg/kg(in normal saline containing 1％ DMSO)were injected intrsperitoneally at 15 min before anesthesia and 3 h after the beginning of anesthesia in groups M1,M2 and M3 respectively,and then the animals inhaled 1.5％ isoflurane for 4 h.At the end of anesthesia,5 rats in each group were chosen and blood samples were taken to perform arterial blood gas analysis and to detect the blood glucose level and expression of phosphorylated Tau(p-Tau)protein in hippocampus.Ten rats in each group were chosen at 14 d after the end of anesthesia and Morris water maze was performed 3 times a day for 5 consecutive days to assess the cognitive function.Then the animals were sacrificed and hippocampi were removed for detection of p-Tau expression by Western blot.Results There were no significant differences in the parameters of arterial blood gas analysis and blood glucose level among the 5 groups(P ＞ 0.05).Compared with group C,the escape latency at 3-5 d was significantly prolonged,the probe time was significantly shortened,and the expression of p-Tau protein was up-regulated in groups I and M1(P ＜0.05),and no significant change was found in the indexes mentioned above in groups M2 and M3 (P ＞0.05).Compared with groups 1 and M1,the escape latency at 2-5 d was significantly shortened,the probe lime was significantly prolonged,and the expression of p-Tau protein was down-regulated in groups M2 and M3 (P ＜ 0.05).There were no significant differences in the indexes mentioned above between groups I and M1,and between groups M2 and M3(P ＞ 0.05).Conclusion Melatonin(10 and 20 mg/kg)can improve isoflurane anesthesia-induced cognitive dysfunclion in aged rats,which nay be related to inhibition of hyperphosphorylation of Tau protein in hippocampus.

Influence of bear bile on rat hepatocarcinoma induced by diethylnitrosamine / 药学学报

To investigate the influence of bear bile on rat hepatocarcinoma induced by diethylnitrosamine (DEN), a total of 40 rats were randomly divided into 4 groups: normal control group, model group, and two bear bile treatment groups. The rat liver cancer model was induced by breeding with water containing 100 mg x L(-1) DEN for 14 weeks. The rats of the bear bile groups received bear bile powder (200 or 400 mg x kg(-1)) orally 5 times per week for 18 weeks. The general condition and the body weight of rats were examined every day. After 18 weeks the activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin (TBIL) were detected. Meanwhile, the pathological changes of liver tissues were observed after H&E staining. The expression of proliferative cell nuclear antigen (PCNA) and a-smooth muscle actin (alpha-SMA) in liver tissue were detected by immunohistochemical method. After 4 weeks the body weights of rats in normal group were significantly more than that in other groups (P < 0.05); and that in the two bile groups was significantly more than that in the model group. Compared with normal group, the level of serum glutamic-pyruvic transaminase and total bilirubin increased significantly in other groups; compared with model group, these two indexes decreased significantly in two bile groups. Hepatocellular carcinoma occurred in all rats except for normal group; there were classic cirrhosis and cancer in model group while there were mild cirrhosis and high differentiation in two bile groups. There were almost no expressions of PCNA and alpha-SMA in normal group while there were high expressions in model group; the two bile groups had some expressions but were inferior to the model group, and alpha-SMA reduced markedly. It indicated that bear bile restrained the development of liver cancer during DEN inducing rat hepatocarcinoma, which may be related to its depressing hepatic stellate cell activation and relieving hepatic lesion and cirrhosis.

Effects of isoflurane anenthesia on myocyte enhancer factor 2 signaling pathway in neonatal rat hippocampus / 中华麻醉学杂志

Objective To investigate the effects of isoflurane anenthesia on myocyte enhancer factor 2(MEF2) signaling pathway in neonatal rat hippocampus. Methods Twenty-four 5-day-old SD rats of both sexes,weighing 10-13 g, were randomly divided into 2 groups ( n = 12 each): control group (group C) and isoflurane group (group I). In group I, 1.5% isoflurane in 100% O2 was inhaled for 6 h. Group C received no treatment.Three rata in each group were sacrificed at 2, 4, 6 h of isoflurane anenthesia and 24 h after isoflurane anenthesia (T1-4), and the hippocampi removed for determination of MEF2 mRNA, synGAP Ⅰ mRNA, Arc mRNA and synapsinⅠ mRNA expression (by PT-PCR) and synapsin Ⅰ protein expression (by Western blot).Results Compared with group C, the expression of MEF2 mRNA, synGAP Ⅰ mRNA, Arc mRNA and synapsin Ⅰ mRNA at T1-3 and synapsin Ⅰ protein at T2-4 was up-regulated in group I ( P ＜ 0.05). Conclusion Inhalation of anaesthetic concentration of isoflurane may affect synapse formation during the development of central nervous system by actirating hippocampal MEF2 signaling pathways in neonatal rats.

Isoflurane enhances the expression of cytochrome C by facilitation of NMDA receptor in developing rat hippocampal neurons in vitro / 华中科技大学学报（医学）（英德文版）

This study examined the effects of clinically relevant concentrations of isoflurane on the amplitude of NMDA receptor current (I(NMDA)) and the expression of cytochrome C in cultured developing rat hippocampal neurons. The hippocampi were dissected from newborn Sprague-Dawley rats. Hippocampal neurons were primarily cultured for 5 days and then treated with different concentrations of isoflurane [(0.25, 0.5, 0.75, 1 minimum alveolar concentration (MAC))]. The peak of I(NMDA) was recorded by means of the whole cell patch clamp technique. The cytochrome C level was detected by Western blotting and quantitative real-time PCR. Our results showed that isoflurane (0.25, 0.5, 0.75 and 1 MAC) potentiated the amplitude of I(NMDA) by (116±8.8)%, (122±11.7)%, (135±14.3)% and (132±14.6)%, respectively, and isoflurane increased the mRNA expression of cytochrome C in a concentration-dependent manner. The cytochrome C mRNA expression reached a maximum after 0.5 MAC isoflurane stimulation for 6 h (P<0.05). It was concluded that isoflurane enhances the expression of cytochrome C in cultured rat hippocampal neurons, which may be mediated by facilitation of NMDA receptor.